Introduction Disease relapse and infection cause significant morbidity and mortality after allogeneic HSCT for AML and MDS. Wilms' tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are both commonly overexpressed in these conditions, and are attractive targets for immunotherapy. We have assessed the safety of a novel combination of tumour associated antigen (TAA) specific and multipathogen (MP) specific T cells administered prophylactically after HSCT in a phase 1 trial. Methods Patients were eligible for the study if WT1 or PRAME gene expression was elevated as determined by droplet digital PCR on diagnostic tumour samples. TAA and MP specific T cells were generated from stem cell donors by stimulating apheresis-derived mononuclear cells with autologous antigen presenting cells expressing tumour, viral or fungal antigens. T cells specific for CMV, EBV and Aspergillus antigens were produced separately and pooled in equal parts into a MP product. Patients received 1 infusion of MP specific T cells and up to 4 infusions of TAA specific T cells at 4-weekly intervals dosed at 2x107/m2, from 28 days post HSCT. Results Seven HSCT recipients have received a total of 26 T cell infusions to date. Median age was 49 years (range 26-67), disease AML (n=4) or high risk MDS (n=3), conditioning myeloablative (n=6) or reduced-intensity (n=1), donor source sibling (n=4) or matched unrelated (n=3). Median expression of WT1 on diagnostic bone marrow tissue was 1464 copies/104 copies of ABL (0-3870), PRAME 131 copies/104 copies of ABL (4-1670). Mean tumour antigen specificity in the TAA product was 2.2% of CD3+ cells for WT1 and 7.3% of CD4+ cells for PRAME. Mean total pathogen specificity in the MP product was approximately 15% (CMV=4.7% and EBV=5.4% of CD3+ cells, Aspergillus=5.3% of CD4+ cells). Patients received WT1 specific (n=3), PRAME specific (n=3) or both WT1 and PRAME specific T cells (n=1). All patients received MP specific T cells. No immediate infusion-related adverse events were reported. At the time of report, at a median of 375 days post-transplant (80-847), 5 out of 7 patients remain alive. Four patients remain in complete disease remission without graft versus host disease (GVHD). One patient did not proceed after 3 of 5 planned infusions after developing chronic lung GVHD but remains in disease remission. There have been 2 deaths (progressive disease and multiorgan failure). The patient with progressive disease had MDS with complex cytogenetics with evidence of persistent disease pre and post-HSCT, prior to T cell infusions. The patient with multiorgan failure had multiple post-transplant complications including bacterial sepsis, hepatic venoocclusive disease and grade 3 acute GVHD of the gut prior to infusion. Patients had low level viral reactivation (CMV n=3, EBV n=5, BKV n=3, HHV6 n=2), however none required treatment and there were no cases of viral tissue disease or EBV post-transplant lymphoproliferative disorder. There were no invasive fungal infections. Conclusion Prophylactic infusions of donor derived WT1/PRAME specific and multipathogen specific T cells post HSCT are well-tolerated and associated with low rates of infection and relapse in patients treated to date. Disclosures No relevant conflicts of interest to declare.